Biosynthesis of peptide antibiotic Daptomycin
Table of Contents
Introduction 3
Discussion 3
Conclusion 8
References 9
Introduction
Streptomyces roseosporus produces a peptide antibiotic that is cyclic in nature and made up of 13
amino acids. The antibiotic is known as Daptomycin and is effective against a wide variety of
gram-positive bacteria. The antibiotic being highly effective in combating diseases caused by
gram-positive organisms, there is a great demand for creating industrial strains of Streptomyces
roseosporus that would be able to produce high amounts of this antibiotic. This study will shed
light on the biosynthetic pathway that leads to the formation of Daptomycin by Streptomyces
roseosporus and the would also focus on the various ways that can be used to bring about strain
improvement in the organism so as to ensure higher production of Daptomycin.
Discussion
In Streptomyces roseosporus, Daptomycin is produced by NRPS or non-ribosomal peptide
synthetase. NRPS is a holoenzyme comprising to three subunits. The three subunits are encoded
by the genes dptA, dptBC and dptD. These three genes are again responsible for the
incorporation of specific amino acids into the peptide chain of Daptomycin. The antibiotic
belongs to the family of acidic lipodepsipeptides named the A21978C family. Daptomycin is a
cyclic antibiotic that has a total of 13 amino acids, 10 among them form a cyclic ring where the
amino acids are connected to each other via ester bonds and the rest 3 amino acids form a side
chain, which is attached cyclic ring. For Streptomyces roseosporus to produce daptomycin, the
fermentation medium is provided with a decanoic acid. The decanoic acid drives the biosynthetic
reaction to the production of a decanoyl product, which acts as a precursor of the cyclic ring of
Daptomycin (Ng et al., 2014). Although daptomycin is exclusively produced by Streptomyces
roseosporus, similar antibiotics are also produced by Streptomyces coelicolor and Streptomyces
fradiae.
Recently a number of NMR studies have been conducted in order to identify the biologically
active conformation of Daptomycin. The complex nature of the daptomycin molecule has made
it difficult for researchers to decipher the biosynthetic pathway used by Streptomyces
roseosporus in order to produce this antibiotic. The NRPS in S. roseosporus employs a
thiotemplate mechanism to produce Daptomycin. It is already known that NRPS is a holoenzyme
and comprises of three subunits; each of these subunits can be divided into domains. The
domains are responsible for adenylation, condensation and thiolation. All these domains function
in a coordinated manner to recognise the correct amino acids and assemble them in the right
order to form Daptomycin. The various domains within the subunits of NRPS have a variety of
functions in addition to the ones mentioned above. Firstly, these domains might serve to activate
Kynurenine or Ornithine that are non-proteinogenic amino acids (Liao et a...
